The long range goal of this project is to understand at the biochemical level how thymus-derived (T) lymphocytes recognize and respond to antigens. Our approach has been to develop a murine T lymphocyte proliferation assay so that we could bring to bear on this problem the extensive knowledge that exists on the genetics and serology of the mouse major histocompatibility complex (MHC), a region which codes for gene products involved in many immunological functions. During the past year we have demonstrated that the genetic control exerted by immune response (Ir) genes of the MHC is expressed in our assay system and that antibodies directed against I region gene products (Ia antigens) can block the T lymphocyte proliferation. Current work is focusing on the relationship between Ir gene products and the Ia antigens as well as the mechanism by which the antibodies inhibit proliferation.